Antithyroid drug carbimazole and its analogues: synthesis and inhibition of peroxidase-catalyzed iodination of L-tyrosine.
Synthesis and biological activity of the antithyroid drug carbimazole (CBZ) and its analogues are described. The introduction of an ethoxycarbonyl group in methimazole and its selenium analogue not only prevents the oxidation to the corresponding disulfide and diselenide but also reduces the zwitterionic character. A structure-activity correlation in a series of CBZ analogues suggests that the presence of a methyl substituent in CBZ and related compounds is important for their antithyroid activity.
Das
Debasis
D
Department of Inorganic & Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India.
Roy
Gouriprasanna
G
Mugesh
Govindasamy
G
D013956:Antithyroid Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002231:Carbimazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis / Q000187:drug effects; D003198:Computer Simulation; D054879:Halogenation / Q000187:drug effects; D015394:Molecular Structure; D009195:Peroxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism*
D013956:Antithyroid Agents; D014443:Tyrosine; D002231:Carbimazole; D009195:Peroxidase